Decrease In Drug Release Rate Research Articles

Development And Components Of Chitosan Primarily Based Microspheres Of Glibenclamide

Development And Components Of Chitosan Primarily Based Microspheres Of Glibenclamide

Sprayable ciprofloxacin-loaded poloxamer hydrogels for wound infection treatment.

Topical antimicrobial treatments for severe burns and chronic wounds provide effective treatment against infections, but cause pain and discomfort with application. This study aimed to develop an antimicrobial topical formulation comprising thermoreversible poloxamers (Pluronic F127 and F68) and a broad-spectrum antimicrobial agent (ciprofloxacin hydrochloride, CH), that could be sprayed to eliminate application pain while maintaining antimicrobial activity. Formulations were characterized to determine their sprayability under cold conditions, gelation temperature, final storage modulus at skin temperature, drug release profile, ex vivo permeation through impaired porcine skin, and inhibition against common bacterial pathogens that colonize wounds. All cold formulations were sprayable from simple hand-held, pump-action sprayers due to their low viscosity. Upon heating, 17 and 20% Pluronic F127 formulations produced hydrogels eight to ten degrees below skin temperature, independent of ciprofloxacin loading. Increasing concentrations of Pluronic F127 increased the final storage modulus and viscosity of the gels, while inclusion of Pluronic F68 reduced these properties, showing that hydrogel rheological properties at skin temperature can be tuned via choice of formulation. Drug release was directly correlated to the rheological properties, with stiffer gels resulting in a decrease in drug release rate. Overall, gels released about 65-90% of their load within 12 hours. Ex vivo skin permeation demonstrated that drug was well retained in impaired porcine skin, which is desired to continuously treat bacteria localized to the wound. A well-diffusion assay indicated that the hydrogels had greater bacterial inhibition against Pseudomonas aeruginosa, Escherichia coli, and two strains of Staphylococcus aureus when compared to commercial controls. Overall, the results show the potential of CH-loaded poloxamer formulations as suitable sprayable topical dressings to deliver antimicrobials directly to wounds.

Design and In-Vitro Evaluation of Compressed Kollidon® SR Based Naproxen Sodium Microcapsule: Effect of Talc

Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic antipyretic properties. In this research work, naproxen sodium was encapsulated by solvent-evaporation technique using kollidon® SR as coating polymeric material to prolong the therapeutic duration of the drug. Four different concentrations of talc were used as additives to see the changes in drug release pattern from the compressed microcapsules. Scanning Electron Microscopy (SEM) was applied to study size and surface morphology of prepared microcapsules. UV-spectrophotometric method was applied to calculate the drug loading efficiency and the performance of the prepared dosage form was evaluated in terms of in-vitro dissolution studies according to USP paddle method (type 2) in 400 ml in phosphate buffer (pH 6.8) for 8 hours at 370 ± 50 C temperature at 50 rpm. Release of naproxen sodium from the compressed microcapsules was found to follow hixon crowell mechanism (R2=0.99). Hixon equation was used to calculate the release exponent value (n) which indicates the drug release behavior and the mean dissolution time T50% (MDT) for release rate. The surfaces of the microcapsules became smoother with the increase in talc amount and simultaneously decrease in drug release rate.
 Keywords: Naproxen sodium, Kollidon® SR, microcapsule, emulsion solvent evaporation technique, MDT (Mean Dissolution Time)

Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery.

Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.

Formulation and Evaluation of Sustained Release Stavudine Microspheres by Ionotropic Gelation Method

As a novel drug delivery system, microspheres improve the efficacy of a drug, increase the time of action, lower the number of times in which a dosage form needs to be administered, and to increase patient compliance. Oral administration side effects such as gastric irritation are lessened through the use of microspheres. Ionotropic gelation was used to create HPMC K15M, Guar gum, and Carbopol 934 microspheres with different concentrations of Carbopol 934 polymer. Cross-linking was accomplished with the use of calcium chloride. In order to conduct a systematic evaluation of all the preparations, we performed various tests: morphology, FTIR, DSC, entrapment efficiency, size, microsphere size, and in-vitro drug release. The discrete, free-flowing, and spherical particles of prepared Stavudine microspheres were found. In compliance with standards, the mean particle size was in the range of 72.64 to 95.22 percent. In vitro drug release studies were performed in phosphate buffer solution with a pH of 6.8. As the concentration of sodium alginate and calcium chloride increased, the percentage of drug release was reduced. In the case of F9 formulation, which contained Stavudine, the decreased drug release rate was obtained via carbopol 934(1:3), sodium alginate, and calcium chloride. Conclusively, the present study shows that Stavudine microsphere preparation and formulation F9 are successful. Stavudine microspheres must be prepared in order to preserve an effective drug concentration in serum for a long time, while reducing gastrointestinal irritation.

Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory diseases. However, the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the lung. In this study, we designed a lipid-coated genistein nanocrystals (Lipo-NCs) formulation to achieve enhanced efficiency of local pulmonary delivery. The Lipo-NCs were fabricated by modifying genistein nanocrystals (NCs) with phospholipid membrane through thin film hydration following the homogenization method. The prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked NCs. Our results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid coating. Furthermore, the macrophages clearance was also impeded by this Lipo-NCs formulation. In vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of Lipo-NCs. The pharmacokinetic study displayed that the AUC(0-t) values of Lipo-NCs were 1.59-fold lesser than those of the NCs group, indicating a reduced systemic absorption. In conclusion, this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance, and thus enhancing drug concentration in lung by pulmonary delivery.

Controlled release of paroxetine from chitosan/montmorillonite composite films

Controlled drug delivery studies popular in pharmaceutical area; polymeric composites prepared with clay has a great potential importance in drug release studies. The aim of the study is to produce biocoposite material suitable for controlled release of Paroxetine Hydrochloride.In this study, chitosan/clay/paroxetine (CS/MMT/PHH and CS/NaMMT/PHH) composite films were prepared to investigate drug release properties of paroxetine (PHH). Films containing various amounts of clay (MMT/NaMMT) (0, 0.1, 0.2, 0.4 g) and glycerol (0.25, 0.50) were prepared by solvent casting method. The structural properties of drug-containing and non-drug containing films were characterized by FT-IR and SEM analysis. The release studies of PHH were done in vitro and pH 7.4 and at 37 °C temperature. The highest percent of drug release was observed with CS/PHH film after 170 h (69%). It was observed that the drug release profiles of chitosan films containing clay (MMT or NaMMT) were better than films without clay. In order to investigate the drug release mechanism, Korsmeyer-Peppas, Higuchi, Zero and First order kinetic models were used.It was determined that release kinetics of the most of films fit the Korsmeyer-Peppas model, and according to this model, drug release occurs through two mechanisms, swelling-controlled and diffusion-controlled. It has been observed that all films containing clay have long-term drug release. Increasing in clay ratio in the composite, caused decrease in drug release rate. PHH loaded CS/MMT/PHH and CS/NaMMT/PHH films showed steady and prolonged drug delivery. Results indicated that prepared CS/MMT/PHH and CS/NaMMT/PHH films has a potential to act as suitable carrier for drugs.

FORMULATION AND EVALUATION OF DRUG RELEASE PROFILE OF HYDROPHILIC POLYMER BASED INDOMETHACIN PROLONG RELEASE MATRIX TABLETS

An oral modied release dosage forms have always been more effective therapeutic alternative to conventional dosage forms. The present invention is directed to a modied release pharmaceutical composition of indomethacin by using hydrophilic release retardant polymers like HPMC K15M, Na CMC alone or in combination. Matrix embedded prolong release tablet formulations of Indomethacin were prepared by wet granulation technique and evaluated for tablet properties such as the thickness, hardness, friability, weight variation, drug content, drug release kinetics and in vitro release studies. The inuence of drug polymer ratio on drug release was studied by dissolution test. The FTIR studies showed no interactions among drug and polymers. The tablets formulation (F7 and F8) containing combined polymers of HPMC K15M and Na CMC resulted in slower drug release rate form the matrix. So, it can be concluded that Indomethacin prolong release tablets using HPMC K15M and Na CMC as the retardant has successfully extended the release of indomethacin from its formulations. The mixing of two cellulose polymers, ionic and non-ionic, for the formulation of hydrophilic matrices, resulted in a valuable decrease in drug release rate. All the formulations showed KorsmeyerPeppa’s model as a best t.

HPMC-Eudragit-Based Gastro-retentive Hydrodynamically Balanced System—Suitable for Sparingly Soluble and Freely Soluble Drugs: an In Vitro Study

In this study HPMC-eudragit based hydrodynamically balanced capsules of two model drugs; propranolol HCl and ofloxacin were prepared with the aim to have the gastric retention of the systems for longer periods of time with desired sustained/ controlled drug release. Gastro-retentive capsules were prepared by simple physical blending of various low density polymers and filling into capsules. These capsules were subjected to in vitro buoyancy/ matrix integrity and dissolution studies. Weight variation, content uniformity test, UV spectral analysis and placebo interaction studies were also performed. Preliminary studies revealed that high soluble drug required higher polymer ratios to sustain drug release and maintain matrix integrity/ buoyancy than low soluble drug. In both the cases, with increase in HPMC and eudragit S100 levels there was an increase in matrix integrity and decrease in drug release rate, however much higher levels of eudragit S100 decreased matrix integrity and buoyancy. Lactose (release rate modifier) decreased matrix integrity, buoyancy and increased drug release. Mechanism of release in the both cases was found to be anomalous "non-fickian". From this research and the literature available on the eudragit and HPMC matrix systems, it is evident that different categories of drugs (suitable for gastric retention), ranging from freely soluble to sparingly soluble can be suitably formulated as HPMCeudragit based GR HBS capsules with desired drug release characteristics, provided no chemical instability/ incompatibility occurs between the drug and the polymers.

Design and evaluation of dental films of PEGylated rosin derivatives containing sparfloxacin for periodontitis

Objective: In this study, PEGylated rosin derivatives (PRDs) namely D1 and D2 were synthesized and evaluated for their application to produce sustained-release antibacterial films containing sparfloxacin for periodontitis.Significance: PRDs are biodegradable and biocompatible, and therefore sustained-release dental implant of PRD-sparfloxacin can provide an effectual treatment for periodontitis.Methods: Films were produced by solvent casting technique and characterized for morphology, swelling-index, in vitro degradation and drug release kinetics. The impact of type of PRD, concentration of PRDs, and addition of plasticizer (dibutyl phthalate) on various film properties was evaluated. The films were also subjected to stability study at 30 °C and 40 °C for 90 days.Results: Both D1 and D2 produced smooth and non-porous films with sparfloxacin. The D1 films, due to lower amount of polyethylene glycol 400 in D1, exhibited lower swelling-index, slower degradation, and slower drug release compared to D2 films. An increase in PRDs concentration decreased swelling-index, prolonged degradation time, and decreased drug release rate of films; addition of plasticizer showed the similar effect. At pH 7.6, D1 and D2 films showed complete degradation at the end of 58 and 51 days, respectively. At the end of 21 days, D1 and D2 films released 41.85% and 61.53% sparfloxacin, respectively. The drug release from D1 films followed Higuchi square-root kinetics, while D2 films released drug by the zero order kinetics. The stability conditions did not significantly alter PRDs-film properties.Conclusion: Results revealed that PRDs can be used successfully to produce sustained-release antibacterial films containing sparfloxacin for the treatment of periodontitis.

Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation

Objective: The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness.Methods: Sildenafil citrate in situ forming gels were prepared using different grades of Pluronic® (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (Tsol-gel), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725).Results: The Tsol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28–37 °C. Increasing Pluronic® concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration.Conclusion: Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.

Nanoscale patterning of biopolymers for functional biosurfaces and controlled drug release.

We compare the rates of drug release from nanopatterned and flat biodegradable polymer surfaces, and observe significantly lower release rates from the nanopatterned surfaces. Specifically, we nanopattern poly(l-lactic acid) (PLLA), a biodegradable polymer frequently used for fabricating drug-eluting coronary stents, through microtransfer molding and solvent casting and investigate the nanopattern's impact on the release of sirolimus, an immunosuppressant agent, coated on the PLLA surface using high performance liquid chromatography/mass spectrometry. We find that PLLA surfaces nanopatterned with 750 nm-pitch nanocup or nanocone arrays exhibit drug release rates significantly lower (25-30%) than that of the flat surface, which is counter-intuitive given the nanopattern-induced increase in their surface areas. Based on diffusion and meniscus curvature minimization analyses, we attribute the decreased drug release rate to the incomplete wetting of the nanopatterned surface. These results provide new insights on how the surface nanopatterning of biomaterials can functionalize the surface and tailor the release kinetics of therapeutic agents coated on it for controlled drug elution.

Effect of pore size of three-dimensionally ordered macroporous chitosan–silica matrix on solubility, drug release, and oral bioavailability of loaded-nimodipine

Objective: To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan–silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug.Methods: 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated.Results: With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively.Conclusion: Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.

Decreased Core Crystallinity Facilitated Drug Loading in Polymeric Micelles without Affecting Their Biological Performances.

Cargo-loading capacity of polymeric micelles could be improved by reducing the core crystallinity and the improvement in the amount of loaded cargo was cargo-polymer affinity dependent. The effect of medium chain triglyceride (MCT) in inhibiting PCL crystallization was confirmed by DSC and polarized microscope. When incorporating MCT into polymeric micelles, the maximum drug loading of disulfiram (DSF), cabazitaxel (CTX), and TM-2 (a taxane derivative) increased from 2.61 ± 0.100%, 13.5 ± 0.316%, and 20.9 ± 1.57% to 8.34 ± 0.197%, 21.7 ± 0.951%, and 28.0 ± 1.47%, respectively. Moreover, the prepared oil-containing micelles (OCMs) showed well-controlled particle size, good stability, and decreased drug release rate. MCT incorporation showed little influence on the performances of micelles in cell studies or pharmacokinetics. These results indicated that MCT incorporation could be a core construction module applied in the delivery of hydrophobic drugs.

Preparation and characterization of cetirizine intercalated layered double hydroxide and chitosan nanocomposites

The syntheses and characterization of Zn–Al layered double hydroxide (LDH) and chitosan nanocomposits are reported in the present paper. By increasing chitosan concentration, the crystallite growth is inhibited in both directions a and c. Afterward, cetirizine-intercalated LDH was synthesized. According to XRD patterns, increase in basal spacing indicated that cetirizine anions were intercalated into LDH. In-vitro drug release experiments have been investigated. On the basis of the release profiles, it was found that increase in chitosan concentration causes in decrease in drug release rate. Therefore, chitosan concentration can be adjusted to control the rate of the drug release.

In Vitro Liberation of Indomethacin from Chitosan Gels Containing Microemulsion in Different Dissolution Mediums

The objective of this research is to outline the liberation of indomethacin from different chitosan gels containing O/W microemulsion. The influence of surfactant, sodium lauryl sulfate, in two concentrations (0.5% and 0.75%, w/w) was determined in dissolution medium on the release of indomethacin, which was used as poor water-soluble model drug. Chitosan gels were prepared in four different concentrations of chitosan-1%, 1.5%, 2%, and 3% (w/w). Microemulsion enhanced the liberation of the indomethacin from chitosan gels into all dissolution mediums. Adding the surfactant into phosphate-buffered saline decreased the amount of liberated indomethacin from microemulsion, gel mixture, but increased the drug liberation from pure chitosan gels. It was detected that with the increased concentration of chitosan in the samples, the amount of indomethacin liberated (p < 0.05) also increased. A conclusion was drawn that the liberation of indomethacin from chitosan gels was influenced by increased pH of the samples. The high viscosity induced a higher release of indomethacin from 3% (w/w) chitosan hydrogel at pH 5.8 as compared with 3% (w/w) chitosan hydrogel at pH 3.8. The highest percentage of released indomethacin was determined when a mixture of microemulsion gel with higher chitosan content was used.

Surelease as granulating liquid in preparation of sustained release matrices of ethylcellulose and theophylline

Objectives: Use of Surelease as a granulation liquid in preparation of granules and matrices of theophylline and ethylcellulose was evaluated.Materials and methods: Physical mixtures (at 1:1 or 1:1.5 drug:polymer) were granulated using water, Surelease or diluted Surelease as granulating liquid. The granule characteristics (shape, size, flow rate, mechanical properties, friability and release profile) were studied. Afterwards, matrices were manufactured and their crushing strengths, friability and release profiles were determined.Results: Granulation produced agglomerated particles with better flowability than physical mixtures. Change of granulation liquid from water to Surelease or diluted Surelease led to the marginal increase in size of granules at 1:1 drug:polymer, however, the flow rate and Carr’s index were considerably improved. The hardness, elastic modulus, friability and rate of drug release were not affected by granulation liquid. Increase in polymer content resulted in reduction in size of granules, flow rate, elastic modulus and rate of drug release. However hardness of the granules was unaffected. Granulation process and granulation liquid did not affect the hardness, and dissolution rate of matrices at 1:1 drug:polymer, while the use of Surelease or diluted Surelease as a granulating liquid, increased the hardness and decreased drug release rate at 1:1.5 drug:polymer. Matrices prepared from Surelease or diluted Surelease showed similar characteristics.Conclusions: Surelease is a suitable granulating liquid for preparation of ethylcellulose matrices especially when high amount of polymer is used and could not only improve the flow and compatibility of the granules, but also help in reducing the rate of drug release.

In vitro and in vivo evaluation of novel interpenetrated polymer network microparticles containing repaglinide

Interpenetrated polymer network (IPN) microparticles of sterculia gum and sodium alginate loaded with repaglinide were developed by ionic gelation and emulsion crosslinking method. The drug entrapment efficiency was as high as 91%. FTIR and TG analyses confirmed the crosslinking and IPN formation. Microparticles have demonstrated the drug release up to 24h depending upon type of crosslinking agents; the glutaraldehyde treatment of ionically crosslinked microparticles has resulted in decreased drug release rate. The in-vivo anti-diabetic activity performed on streptozotocin induced diabetic rats indicated that the pristine repaglinide has shown maximum percentage reduction of elevated blood glucose within 3h and then the percentage reduction in blood glucose was decreased. In the case of rats treated with KA8 IPN microparticles, percentage reduction of elevated glucose was slow as compared to pristine drug within 3h, but it was gradually increased to 81.27% up to 24h.

Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: Comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3

The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from - and erosion rate of - 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated using factorial designed experiments. Furthermore, the mechanism of release in Ensure Plus(®), a nutrition drink similar in composition to the FDA standard meal, was investigated by studying tablet swelling using texture analysis. Altering dip speed has negligible effect on release and erosion rates. Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s viscosity tablets compared to the 4000 and 15,000 mPa s viscosity tablets. The investigation using texture analysis indicates that Ensure Plus(®) becomes rate-limiting for caffeine release from HPMC tablets by forming a hydrophobic barrier around the tablets. The barrier decreases tablet water permeation, which decreases erosion rate in 100 mPa s viscosity tablets, swelling in 15,000 mPa s viscosity tablets and caffeine release from both tablets. This observed interaction between Ensure Plus(®) and the HPMC tablets may translate into decreased drug release rate in the fed stomach, which may decrease the amount of drug available for absorption in the small intestine and thus reduce systemic drug exposure and maximum plasma concentration.

The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets

Context: Mini-tablets are compact dosage forms, typically 2–3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.Objective: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.Methods: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL™ K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.Results and Discussion: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.Conclusion: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.